1. Field of the Invention
The present invention generally relates to plant-derived polyphenolic compounds, inhibitors of reactive oxygen species (ROS) and compositions thereof and methods for treating, preventing, or inhibiting cancer, such as pancreatic cancer.
2. Description of the Related Art
Pancreatic cancer is the fifth leading cause of cancer death in the United States Cures for this type of cancer are unusual with the cancer recurring as metastatic disease in most cases after the removal of the primary tumor at surgery. See DiMagno EP, et al. (1999) Gastroenterology 117:1464-1484; and Todd K E, et al. (1999) Pancreatic adenocarcinoma. TEXTBOOK OF GASTROENTEROLOGY. Philadelphia: Lippincott Williams & Wilkins, p. 2178-2192.
The development of tumors results from an imbalance between cell proliferation and cell death, apoptosis, and necrosis. See Thompson C B (1995) Science 267:1456-1462. Apoptosis is an active form of cell suicide characterized by a set of events including chromatin condensation, plasma membrane blebbing, cell shrinkage, DNA cleavage by specific endonucleases, and translocation of phosphatidylserine from the inner leaflet of the plasma membrane to the outer leaflet. See Thompson C B (1995); and Cohen J J (1993) Immunol. Today 14:126-130. Phosphatidylserine serves as a marker for macrophages to recognize apoptotic cells and phagocytize them.
There is increasing evidence that one of the major underlying defects in most cancers is an inhibition of normal apoptosis. See Thompson C B (1995) and Cohen J J (1993). Furthermore, treatments such as radiation and chemotherapy act to kill tumor cells and induce tumor shrinkage by causing apoptosis of cancer cells. Apoptosis can additionally be caused by removal of growth factors, the action of specific cytokines, i.e. TNFα, IL-1β, and Fas ligand, and detachment of cells from their extracellular matrix. Recent reports including our own indicate that some polyphenolic phytochemicals are capable of causing apoptosis in cancer cells. See Mouria M, et al. (2002) Int. J. Cancer 98(5):761-769; Hsieh T C and Wu J M (1999) Exp. Cell. Res. 249:109-115; Huang C, et al. (1999) Carcinogenesis 20:237-242; Islam S, et al. (2000) Biochem. Biophys. Res. Commun. 270:793-797; Sakagami H, et al. (2000) Anticancer Res. 20:271-277; Gupta S, et al. (2000) Toxicol. Appl. Pharmacol. 164(1):82-90; Li H C, et al. (2000) Jpn J. Cancer Res. 91(1):34-40; Paschka A G, et al. (1998) Cancer Lett 130:1-7; Wang I K, et al. (1999) Eur. J. Cancer 35:1517-1525; and Surh Y J (1999) Cancer Letters 140:1-10.
Although induction of apoptosis appears to be a promising therapeutic approach to the treatment of cancer, the intracellular mechanisms of apoptosis are incompletely understood. Thus, a need still exists for compositions and methods for inducing apoptosis and treating cancer.